Question 1 · Hard
A 49-year-old woman is referred because her hs-troponin I has been between 180 and 210 ng/L (99th percentile upper reference limit 16 ng/L) on five occasions over 8 months, always without chest pain. ECG, echocardiogram and coronary CT angiography are normal, and eGFR is 95 mL/min/1.73 m². On the same samples, hs-troponin T is 6 ng/L (99th percentile 14 ng/L) and CK is normal. Re-testing troponin I after treatment with a heterophile blocking reagent gives the same result. After polyethylene glycol (PEG) precipitation, 15% of the troponin I is recovered, against 60-80% for control samples. What is the most likely explanation?
- ATroponin released from diseased skeletal muscle
- BHeterophile antibodies interfering in the assay
- CMacrotroponin: troponin I bound to an autoantibody
- DChronic myocardial injury from hidden heart disease
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Answer: C · Macrotroponin: troponin I bound to an autoantibody
The troponin I is high but stable over months, with no symptoms, normal cardiac imaging and a normal troponin T, which is not the pattern of myocardial injury. PEG precipitates immunoglobulins, so the low recovery shows that most of the measured troponin I is bound to immunoglobulin; this macrotroponin is cleared slowly and builds up in the blood. Heterophile antibody interference is unlikely because the blocking reagent did not change the result. Diseased skeletal muscle can raise troponin T results but not troponin I, and here troponin T and CK are normal. Recognising macrotroponin, by gel filtration if needed, prevents repeated cardiac investigations, and a troponin T assay can be used for this patient in future.
- A: Skeletal muscle disease raises troponin T, not troponin I, and her CK is normal.
- B: The heterophile blocking reagent did not change the result.
- D: Myocardial injury would also raise troponin T, and her heart studies are normal.